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Clinical Chemistry 50: 552-558, 2004. First published January 6, 2004; 10.1373/clinchem.2003.027763
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Right arrow Proteomics and Protein Markers
(Clinical Chemistry. 2004;50:552-558.)
© 2004 American Association for Clinical Chemistry, Inc.

Proteomics and Protein Markers

Prognostic Value of Tubular Proteinuria and Enzymuria in Nonoliguric Acute Tubular Necrosis

Stefan Herget-Rosenthal1,a, Dennis Poppen1, Johannes Hüsing2, Günter Marggraf3, Frank Pietruck1, Heinz-Günther Jakob3, Thomas Philipp1 and Andreas Kribben1

Departments of1 Nephrology and 3 Thoracic and Cardiovascular Surgery, University Hospital, Essen, Germany. 2 Institute for Medical Informatics, Biometry and Epidemiology, Medical School, University of Essen, Essen, Germany.

aAddress correspondence to this author at: Klinik für Nieren - und Hochdruckkrankheiten, Universitätsklinikum Essen, D-45122 Essen, Germany. Fax 49-201-723-5633; e-mail stefan.herget-rosenthal{at}uni-essen.de.

Background: Acute tubular necrosis (ATN) has high mortality, especially in patients who require renal replacement therapy (RRT). We prospectively studied the diagnostic accuracy of the urinary excretion of low-molecular-weight proteins and enzymes as predictors of a need for RRT in ATN.

Methods: In 73 consecutive patients with initially nonoliguric ATN, we measured urinary excretion of {alpha}1- and ß2-microglobulin, cystatin C, retinol-binding protein, {alpha}-glutathione S-transferase, {gamma}-glutamyltransferase, lactate dehydrogenase, and N-acetyl-ß-D-glucosaminidase early in the course of ATN.

Results: Twenty-six patients (36%) required RRT a median of 4 (interquartile range, 2–6) days after detection of proteinuria and enzymuria. Patients who required RRT had higher urinary cystatin C and {alpha}1-microglobulin [median (interquartile range), 1.7 (1.2–4.1) and 34.5 (26.6–45.1) g/mol of creatinine] than patients who did not require RRT [0.1 (0.02–0.5) and 8.0 (5.0–17.5) g/mol of creatinine]. Urinary excretion of cystatin C and {alpha}1-microglobulin had the highest diagnostic accuracies in identifying patients requiring RRT as indicated by the largest areas under the ROC curves: 0.92 (95% confidence interval, 0.86–0.96) and 0.86 (0.78–0.92), respectively. Sensitivity and specificity were 92% (95% confidence interval, 83–96%) and 83% (73–90%), respectively, for urinary cystatin C >1 g/mol of creatinine, and 88% (78–93%) and 81% (70–88%) for urinary {alpha}1-microglobulin >20 g/mol of creatinine.

Conclusion: In nonoliguric ATN, increased urinary excretion of cystatin C and {alpha}1-microglobulin may predict an unfavorable outcome, as reflected by the requirement for RRT.




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